The long-term objective of this research project is to determine whether endogenous enkephalins play a major role as neurotransmitters/neuromodulators of oral ethanol preference. Studies will be performed to determine whether altering the action of endogenous enkephalins changes voluntary ethanol drinking. Specifically, we will examine: 1) the extent to which various opioid receptor antagonists are capable of suppressing voluntary ethanol consumption compared with the consumption of other palatable and nonpalatable substances, 2) whether blocking endogenous opioid receptors, prior to initial exposure to ethanol, deters the initiation and development of voluntary ethanol consumption, and 3) whether increasing the duration of enkephalin action potentiates voluntary ethanol drinking. These experiments will require the use of rats which voluntarily consume large quantities of ethanol. Rats from two genetic lines, which have been bred for oral ethanol preference, will serve as subjects. We also propose to determine whether the central enkephalinergic system differs in rats that display different preferences for oral ethanol. Specifically, we will determine: 1) whether enkephalin and preproenkephalin mRNA content in discrete brain and pituitary regions differs in ethanol-naive rats which have been genetically selected for oral ethanol preference or nonpreference, 2) whether chronic voluntary ethanol drinking, and removal of ethanol following chronic consumption, alters brain and pituitary content of enkephalins and preproenkephalin mRNA, and 3) whether a true correlation exists between brain enkephalin and preproenkephalin mRNA content and the amount of ethanol voluntarily consumed during free-choice drinking. These experiments will require the use of rats which voluntarily consume high or low amounts of ethanol. Rats from four genetic lines, which have been bred for oral ethanol preference or nonpreference, will serve as subjects. The results of the proposed studies should yield additional information regarding the importance of the central enkephalinergic system in mediating the reinforcing properties of ethanol that contribute to the development and maintenance of abnormal alcohol seeking behavior which characterize human alcoholism.